This research will help elucidate mechanisms whereby the shape of the developing embryonic limb is determined. Specifically we are addressing the questions of what determines the assymetry or polarity of its three anatomical axes, the antero-posterior, dorso-ventral and proximo-distal. Experimental evidence suggests the antero-posterior (a-p) axis is controlled by a gradient of some morphogenetic substance whose origin is the mesoderm along the posterior border of the limb. We are investigating the nature of this morphogenetic substance and its effects on limb development. The proximo-distal (p-d) axis is determined in part by the position and outgrowth inducing effects of an apical ectodermal ridge. We are investigating the relationshop between this ridge and the ability of underlying mesoderm to differentiate. Little is known about the control of dorso-ventral polarity. The literature suggests that control resides in the mesoderm at some times during development and in the ectoderm at others. We will perform tissue recombination experiments to verify this and discover when these transitions in site of control occur.